کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6271136 | 1614748 | 2016 | 11 صفحه PDF | دانلود رایگان |
- Icariside II ameliorated cognitive deficits and neuronal morphological damage.
- Icariside II reduced the level of PDE5 in STZ rat.
- Icariside II attenuated the level of Aβ in STZ rat by down-regulation of APP and BACE1 and up-regulation of NEP.
- Icariside II inhibited the overexpression of TNF-α, IL-1β, COX-2 and TGF-β1 induced by STZ.
- Icariside II prevented IκB-α degradation and NF-κB activation induced by STZ.
Beta-amyloid (Aβ) deposition and neuroinflammation are involved in Alzheimer's disease (AD)-type neurodegeneration with cognitive deficits. Phosphodiesterase-5 (PDE5) inhibitors have recently been studied as a potential target for cognitive enhancement by reducing inflammatory responses and Aβ levels. The present study was designed to investigate the effects of icariside II (ICS II), a novel PDE5 inhibitor derived from the traditional Chinese herb Epimedium brevicornum, on cognitive deficits, Aβ levels and neuroinflammation induced by intracerebroventricular-streptozotocin (ICV-STZ) in rats. The results demonstrated that ICV-STZ exhibited cognitive deficits and neuronal morphological damage, along with Aβ increase and neuroinflammation in the rat hippocampus. ICS II improved cognitive deficits, attenuated neuronal death, and decreased the levels of Aβ1-40, Aβ1-42 and PDE5 in the hippocampus of STZ rats. Furthermore, administration of ICS II at the dose of 10 mg/kg for 21 days significantly suppressed the expression of beta-amyloid precursor protein (APP), beta-secretase1 (BACE1) and increased the expressions of neprilysin (NEP) together with inhibited interleukin-1β (IL-1β), tumor necrosis factor (TNF)-α, cyclooxygenase-2 (COX-2) and transforming growth factor-β1 (TGF-β1) levels. In addition, ICS II exerted a beneficial effect on inhibition of IκB-α degradation and NF-κB activation induced by STZ. Taken together, the present study demonstrated that ICS II was a potential therapeutic agent for AD treatment.
Journal: Neuroscience - Volume 328, 22 July 2016, Pages 69-79